Blood and tissue filarial nematodes are roundworms that infect humans. These organisms are transmitted via a blood-sucking arthropod vector such as a mosquito, midge, or fly. The filarial nematodes infect the subcutaneous tissues, deep connective tissues, body cavities, and lymphatic system. The life cycles of the filarial nematodes are complex (Figure 53-1). The infective larval stage resides in the insect vector with the adult worm stage, which is the pathogenic form in humans. When the arthropod vector feeds on a human blood meal, the infective larvae are injected into the bloodstream. The larvae are motile and migrate to the lymphatic vessels. The infective larvae grow and develop into the adult gravid worm in the human host over a period of months. The male and female adult worms mate in the definitive human host. The female worm produces large numbers of larvae called microfilariae. Depending on the species, the microfilariae may maintain the egg membrane as a sheath or may rupture the egg membrane, resulting in an unsheathed form. These parasites can reside in the host for many years and cause chronic, debilitating conditions and severe inflammatory responses. Identification of the various species is based on the morphology of the microfilaria, the periodicity (defined circadian rhythm), and the location within the human host. Microfilariae morphologic characteristics are important in the identification and include the presence or absence of the sheath and the presence and arrangement of the nuclei in the tail of the worm (Figure 53-2). A comparison of the morphologic characteristics of the pathogenic filarial worms is depicted in Figure 53-3. Diagnosis of infection is based on the identification of the microfilariae in the blood or tissue of the host.